Pain Management and Older Adults

1. Pain Management and Older Adults Module development: Lynne E. Kallenbach MD Asst. Professor of Medicine

2. Objectives Demographics of pain in older adults Overview of pain physiology Discussion of appropriate use of opioids in older adults Discussion of other pain treatment modalities for older adults Overview of ACOVE indicators on pain management

3. Persistent Pain Painful experience continuing for prolonged period of time May or may not be associated with a recognizable disease process Common in older adults - 1 in 5 older Americans are taking analgesic meds regularly - 63% of them had taken prescription pain meds for >6 months Will generally be discussing persistent pain in older adults and mostly in outpatient setting� different discussions apply to acute trauma pain management / post-op pain, etc� In LTC: 71 % reported pain, 34% constant - >1/2 had daily intermittent pain ---only 15% had gotten pain meds within the last 24hrs Will generally be discussing persistent pain in older adults and mostly in outpatient setting� different discussions apply to acute trauma pain management / post-op pain, etc� In LTC: 71 % reported pain, 34% constant - >1/2 had daily intermittent pain ---only 15% had gotten pain meds within the last 24hrs

4. Persistent Pain Degenerative joint disease Chronic back pain Myofascial pain syndromes Peripheral vascular disease Neuropathic pain Post-stroke syndromes Headache Crystal arthropodies Osteoporosis with fracture Oral pathology RLS

5. Persistent Pain Very little research focuses on pain syndromes in the elderly Multiple treatment options are available Opioid use can be safe Do not have much information regarding effect of age alone on most complex pain functionsDo not have much information regarding effect of age alone on most complex pain functions

6. ACOVE Indicators Assessing Care of Vulnerable Elders Comprehensive set of quality assessment tools for ill older adults - Covering domains of prevention, diagnosis, treatment, and follow up - Both hospital based and ambulatory based indicators Designed to evaluate health care at system level rather than individual level

7. ACOVE Indicator ALL vulnerable elders should be screened during the initial evaluation period BECAUSE older people commonly have pain that goes unrecognized by health care providers i.e. new patient visiti.e. new patient visit

8. ACOVE Indicator ALL vulnerable elders should be screened for chronic pain every 2 years BECAUSE older people commonly have pain that goes unrecognized by health care providers Optimal screening time has not been studied- this represents the max interval between screenings from ACOVE expert panelOptimal screening time has not been studied- this represents the max interval between screenings from ACOVE expert panel

9. ACOVE Indicator IF a vulnerable elder has a newly reported chronic painful condition THEN treatment should be offered BECAUSE treatment may provide significant relief and improve quality of life and health status

10. Persistent pain In general, pain is under-treated in older adults Untreated pain is associated with - decreased function - depression/ anxiety - sleep disturbances Being used as quality indicator Strong association between chronic pain and impaired ambulation, increased health care utilizationStrong association between chronic pain and impaired ambulation, increased health care utilization

11. Reasons for Undertreatment Both physician and patient based concerns - regulatory - � it�s just because I�m old� - concerns about cost, possible side effects - addiction / tolerance concerns - problems with assessment Independent risk factors for not receiving analgesia : age older than 85, cognitive impairment, ethnic minority status, polypharmacy (>11 meds)Independent risk factors for not receiving analgesia : age older than 85, cognitive impairment, ethnic minority status, polypharmacy (>11 meds)

12. ACOVE Indicator IF a vulnerable elder has a newly reported chronic painful condition THEN a targeted history and physical examination should be initiated within 1 month BECAUSE appropriate treatment of the condition and pain management require that the nature of the condition be understood Pain history Pain assessment Type of pain and modalities availablePain history Pain assessment Type of pain and modalities available

13. Pain Assessment History Can be difficult to assess in demented patients Evaluate pain by self-report (tools below), behavioral, or physiologic measures Most tools / graphs frequently assess pain intensity

14. Assessment Tools Visual Analogue Scales Facial Pain Scales Numeric Rating Scales Verbal Rating Scales Multidimensional tools McGill Pain map May be more of a global view, effect on function Multiple others � at least 12 different behavioral based tools for patients with dementia Pain Assessment questionnaire � what, when, where --- quality, character, how bad ---- what meds have you tried ----? Effects on ADLs Visual analogue scale (VAS)� no pain -------------------------very severe pain VRS � six item descriptors (no pain, mild pain, severe pain, excruciating etc�) Multidimensional tools � more of a 360 degree view - looking at pain disability scale, intensity, location, effect Other tools looking at pain assessment with the MDS and other NH assessment tools � at least 12 behavioral tools are available, article from BMC Geriatrics attempted to determine most reliable and came up with DOLOPLUS2 and PACSLAC � caregiver administered With demented patients look for : change in appetite, change in behavior (tearful, agitated, decreased participation), facial expressions, other verbalizations and vocalizations Pain Assessment questionnaire � what, when, where --- quality, character, how bad ---- what meds have you tried ----? Effects on ADLs Visual analogue scale (VAS)� no pain -------------------------very severe pain VRS � six item descriptors (no pain, mild pain, severe pain, excruciating etc�) Multidimensional tools � more of a 360 degree view - looking at pain disability scale, intensity, location, effect Other tools looking at pain assessment with the MDS and other NH assessment tools � at least 12 behavioral tools are available, article from BMC Geriatrics attempted to determine most reliable and came up with DOLOPLUS2 and PACSLAC � caregiver administered With demented patients look for : change in appetite, change in behavior (tearful, agitated, decreased participation), facial expressions, other verbalizations and vocalizations

16. Faces scale, thermometer scale, verbal rating scale, numerical scaleFaces scale, thermometer scale, verbal rating scale, numerical scale

17. Pain Pain categorized as - Nociceptive * somatic * visceral - Neuropathic

18. Nociceptive Pain Somatic Somatic NS Skin, muscle, soft tissue, bone Easier to localize Sharp, throbbing, constant, aching Visceral Autonomic NS More stretch/ chemical receptors Harder to describe and localize � may be constant or come in waves Cardiac, lung, GI, GU tracts

19. Pain Pathways - Up Stimulation of peripheral nociceptors Travel along small myelinated A and unmyelinated C fibers to DRG Signals travel from dorsal horn to thalamus along spinothalamic tract Then on to the primary and secondary somatosensory cortices, amygdala Primary and secondary� anterior cingulate gyrus, limbic systemPrimary and secondary� anterior cingulate gyrus, limbic system

21. Pain Pathways Descending pathways can modulate activity in dorsal horn � �gating� �Wind-up� phenomenon in DRG NMDA receptor fires in response to repeated pain stimulus Releases glutamate, activating other secondary pain receptors in spinal cord Augmentation of pain stimulus in spinal cord going up Arborization in DRG There is not �wind-up� in all chronic low level pain but when things seem out of control or out of context this may be happening � or with phantom pain Arborization in DRG � signal to different layers of DRG landing in �touch tracts� >>> allodynia NMDA receptor blockers � dextromethorphan, ketamine, methadone, propofolThere is not �wind-up� in all chronic low level pain but when things seem out of control or out of context this may be happening � or with phantom pain Arborization in DRG � signal to different layers of DRG landing in �touch tracts� >>> allodynia NMDA receptor blockers � dextromethorphan, ketamine, methadone, propofol

22. Pain Sensitization occurs with chronic pain Injured/ chronically stimulated nerves fire w/o stimulus Happens when pain inadequately treated over time Can explain why chronic pain may not seem to have direct cause clinically Injured chronically stimulated nerves fire without stimulus � Na+ channels are responsible for this Injured chronically stimulated nerves fire without stimulus � Na+ channels are responsible for this

23. So what works where? Peripheral nociceptors local anesthetics, anti-inflammatories Dorsal horn local anesthetics, opioids, alpha2 antagonists Central opiods, alpha 2 antagonists

24. Modalities for Rx Non- pharmacologic/ Non- systemic Non-opioid - acetominophen - NSAIDs/ COX-2 �I may require caution in older adults - Steroids Opioids Adjunctive (neuropathic) - Anti-convulsants - Steroids - TCAs Interventional modalities APAP � mechanism unknown but thought to act centrally --- toxicity limits dosing NSAID � good for musculoskeletal / bone pain --- may act centrally to modulate pain perception Interventional modalities can include myofascial trigger point injections, joint injections, nerve blocks, surgery, etc�APAP � mechanism unknown but thought to act centrally --- toxicity limits dosing NSAID � good for musculoskeletal / bone pain --- may act centrally to modulate pain perception Interventional modalities can include myofascial trigger point injections, joint injections, nerve blocks, surgery, etc�

25. Non-pharmacologic/ non-systemic Pain education programs Behavioral modification Physical therapy- massage, heat, ice, ultrasound Other exercise therapy Topical analgesics Neurostimulation Behavioral : cognitive behavioral therapy PT : massage, heat, ice, ultrasound Exercise : water therapy has some supporting data for improved pain control with OA � exercise will also improve mood, functional status, gait improvement Neurostim : TENS used ? dataBehavioral : cognitive behavioral therapy PT : massage, heat, ice, ultrasound Exercise : water therapy has some supporting data for improved pain control with OA � exercise will also improve mood, functional status, gait improvement Neurostim : TENS used ? data

26. General Principles Chronic pain needs chronic medicine Stepwise approach Nociceptive pain generally responds to acetominophen, opioids, anti-inflammatories Neuropathic pain responds to neuropathic agents and, less well, to opioids Mechanism: Na+ channel blockade, upregulation of GABA in spinal cord, upregulation of norepi/ serotonin in cord and cortex � all modulate transmission of pain signal on peripheral nerve or in CNS Na+ channel blockade --- lidocaine, valproic acid, tegretol Upregulation of GABA --- gabapentin Other general principles --- don�t forget to assess for mood and anxiety � pain is a whole / remembered experienceNa+ channel blockade --- lidocaine, valproic acid, tegretol Upregulation of GABA --- gabapentin Other general principles --- don�t forget to assess for mood and anxiety � pain is a whole / remembered experience

28. ACOVE Indicator IF a vulnerable elder has been prescribed a nonselective non-steroidal anti-inflammatory drug (NSAID) for the treatment of chronic pain THEN the medical record should indicate whether he or she has a h/o of PUD and, if hx is present, justification of NSAID use should be documented BECAUSE older patient with a hx of PUD who receive NSAIDs are @ significant risk for recurrent disease and complications Risk of bleeding increases with age � hx of upper GIB was greatest predictor of subsequent GIB Relative risk in one study 4.1 for PUD for NSAID users vs. non usersRisk of bleeding increases with age � hx of upper GIB was greatest predictor of subsequent GIB Relative risk in one study 4.1 for PUD for NSAID users vs. non users

29. Case The patient is an 82 year old frail female, hospitalized for pain control after several acute vertebral compression fractures. Outpatient pain management has not been successful. She has lost some weight and has early dementia. Where do you start?

30. Case, cont�d Pain assessment - Including complete H&P - Nature and severity of pain Analgesia history Other considerations? She is started on a continuous morphine IV infusion given chronicity of the pain in the acute phase.

31. A Brief Review� Pharmacodynamics - Change with age * numbers of receptors * sensitivity of receptors * Counter regulatory mechanisms - Increase in receptor response is noted with opioids - Not as well understood as pharmacokinetics Pharmacodynamics may be altered with aging as well � older adults may have more sensitivity to opioids and longer duration of actions (changes in signalling etc�) Pharmacodynamics may be altered with aging as well � older adults may have more sensitivity to opioids and longer duration of actions (changes in signalling etc�)

32. A Brief Review, cont�d Pharmacokinetics - Absorption overall amt unchanged - Distribution increased Vd for lipophilic drugs - Metabolism generally prefer phase 2, less interaction and active metabolites - Elimination decreased renal function Absorption � overall amt unchanged Distribution � increased Vd for lipophilic drugs Metabolism � generally prefer phase 2 pathway, less interaction and active metabolites Elimination � decreased renal function Absorption � overall amt unchanged Distribution � increased Vd for lipophilic drugs Metabolism � generally prefer phase 2 pathway, less interaction and active metabolites Elimination � decreased renal function

33. And now a little about opioids� Bind to one or more of the opiate receptors (mu, kappa, delta) Mu receptor is 7 transmembrance G protein coupled receptor - binding stabilizes the membrane so neuron doesn�t fire Where are the mu receptors? - periphery, dorsal root ganglia of spinal cord, periaqueductal grey of brainstem, midbrain, gut

34. Opioids Metabolism mostly in liver - First pass may take away significant amt of oral drug - But with advanced liver dz, 1st pass is bypassed Metabolism mostly in liver with excretion in kidneyMetabolism mostly in liver with excretion in kidney

35. Opioids �weak� opioids - codeine - hydrocodone - oxycodone �strong� opioids - hydromorphone - fentanyl - morphine

36. Opioids Distribution Hydrophilic * morphine, oxycodone, hydromorphone Lipophilic * fentanyl, methadone

37. Opioids IV- morphine, hydromorphone, fentanyl PO- morphine (LA & SA), oxycodone (LA & SA), hydromorphone, methadone, fentanyl, hydrocodone Transdermal- fentanyl Initial decisions based on - route of administration - need for continuous vs. intermittent dosing - severity of pain LA= long acting SA= short acting LA= long acting SA= short actingLA= long acting SA= short acting

38. Intravenous Opioids Morphine - �gold standard� Fentanyl - synthetic - 80-100 x potency of morphine - no histamine release thus less hemodynamic effect Hydromorphone - semisynthetic morphine derivative

39. Oral Therapy Oxycodone and hydrocodone combinations common - dosing limited by acetominophen content When titrating for relief, will need close follow-up - then can convert short acting needs to long acting needs if required

40. Opioids-Pharmacology All water soluble opioids behave similarly: Cmax is 60-90 minutes after PO dose 30 minutes after SQ or IM 6-10 minutes after IV dose All are conjugated in liver and 90% excreted via the kidney With normal renal fx, all have � life of 3-4 hours, reach steady state in 4-5 � lives Dose breakthrough at the Cmax of the drug � q 1-2 hr for po --- the q4-6 hrs you typically see is not based on kinetics but rather on the APAP limitations Breakthrough prn should be 5-15% of the 24 hr total doseDose breakthrough at the Cmax of the drug � q 1-2 hr for po --- the q4-6 hrs you typically see is not based on kinetics but rather on the APAP limitations Breakthrough prn should be 5-15% of the 24 hr total dose

41. Case, cont�d You are rounding on your patient and note that she seems agitated. Her family has noted that she has been twitching. What is your assessment? What can you do?

42. ACOVE Indicator IF a vulnerable elder is treated for a chronic painful condition THEN s/he should be assessed for a response within 6 months BECAUSE initial treatment is often incompletely successful, and reassessment may be needed to achieve the most favorable outcome. Clearly, in house, this patient is reassessed sooner, but this indicator serves to remind us to reassess outpatients as well given the heterogeneity of responses that may occur and potential side effects of the medications.Clearly, in house, this patient is reassessed sooner, but this indicator serves to remind us to reassess outpatients as well given the heterogeneity of responses that may occur and potential side effects of the medications.

43. Special Notes Morphine - low protein binding - dialyzes off - active metabolite is morphine 6- glucuronide (10%) * accumulates in renal failure and causes neuroexcitation * prolonged CNS effects

44. Case, cont�d Your patient has mildly decreased renal function The twitching is myoclonus related to the metabolites from the morphine You change her to a dilaudid infusion and ultimately to sustained release oxycodone

45. Special Notes Fentanyl - little or no active metabolites - Not dialyzable - Elderly more sensitive to effects lipophilic so larger Vd - Unclear how TD route is affected by low subcutaneous fat Older adults more sensitive to effect � fentanyl is lipophilic so higher VdOlder adults more sensitive to effect � fentanyl is lipophilic so higher Vd

46. Special Notes Hydromorphone - Generally considered to have inactive metabolites - Drug of choice with renal failure

47. Special Notes Oxycodone - Undergoes phase I metabolism - 10% of the metabolites are oxymorphone, which is 14x as strong as oxycodone

48. Special Notes Hydrocodone - Dosing limited by combination agent - half life elimination ~ 4 hours - onset of analgesia ~ 10-20 min

49. Special Notes Methadone binds mu and blocks NMDA receptors highly protein bound older adults may have more free/ active drug highly variable and prolonged half life Phase I metabolism and may prolong the QT interval caution when changing from another opioid to methadone non-linear conversion Can be a very useful medication, especially for patient requiring high doses of opioids, those with cost issues, or those with mixed pain syndromes as has effect against neuropathic pain as well Use some caution in elderly for several reasons � highly protein bound so with decreased albumin in older adults may have more free/ active drug than you expect and also lipophilic so higher Vd Regarding QT issues � be sure to check what other medications patient is on Remember when converting / dosing � there is not a linear equalanalgesic conversion to methadone � for morphine dose up to 100 mg per 24 hrs there is one dosing ratio, 101-200 has another dosing ratio etc� so much more complicated Dose q 8hr rather than tid (dosed ay 7am, 1 pm, 7 pm so overnight left too long)Can be a very useful medication, especially for patient requiring high doses of opioids, those with cost issues, or those with mixed pain syndromes as has effect against neuropathic pain as well Use some caution in elderly for several reasons � highly protein bound so with decreased albumin in older adults may have more free/ active drug than you expect and also lipophilic so higher Vd Regarding QT issues � be sure to check what other medications patient is on Remember when converting / dosing � there is not a linear equalanalgesic conversion to methadone � for morphine dose up to 100 mg per 24 hrs there is one dosing ratio, 101-200 has another dosing ratio etc� so much more complicated Dose q 8hr rather than tid (dosed ay 7am, 1 pm, 7 pm so overnight left too long)

50. Potential opioid side effects Nausea CNS depression/ sedation Pruritis Constipation Delirium Endocrine dysfunction with long term use Sedation is generally seen with opioid na�ve patients and ameliorates over time, usually For patients on chronic opioids, resp. suppression not generally a concern when logically dosedSedation is generally seen with opioid na�ve patients and ameliorates over time, usually For patients on chronic opioids, resp. suppression not generally a concern when logically dosed

51. ACOVE Indicators IF a vulnerable elder with chronic pain is treated with opioids THEN s/he should be offered a bowel regimen or the medical record should document with potential for constipation or explain why bowel treatment is not needed BECAUSE opiate analgesics produce constipation that may cause severe discomfort and may contribute to inadequate pain treatment because patients may then minimize analgesic use This is the side effect that does NOT ameliorate with time� Exacerbated by immobility and dehydration, which are common in this age group This is the side effect that does NOT ameliorate with time� Exacerbated by immobility and dehydration, which are common in this age group

52. Other Notes Certain opioids generally avoided in the elderly - propoxyphene not any more effective, more cognitive side effects - meperidine metabolite with long T � and no analgesic qualities, �stacking� phenom >>> lower seizure threshold - tramadol lowers seizure threshold, increases risk for interaction >>> serotonin syndrome Meperdine � metabolized to normeperidine which has long half life and no analgesic qualities so end up �stacking� up the metabolite with no added benefit � this metabolite lowers the seizure threshold Tramadol � opioid receptor binding + norepi and serotinergic reuptake inhibition --- lowers seizure threshold and increases risk for serotonin syndrome with other medicationsMeperdine � metabolized to normeperidine which has long half life and no analgesic qualities so end up �stacking� up the metabolite with no added benefit � this metabolite lowers the seizure threshold Tramadol � opioid receptor binding + norepi and serotinergic reuptake inhibition --- lowers seizure threshold and increases risk for serotonin syndrome with other medications

54. Opioids and Older Adults Appropriate for persistent pain, both malignant and non-malignant Generally utilized for non-malignant pain after other options have failed

55. Opioids and Older Adults Should always be accompanied by a bowel regimen May need to clarify with patients and facilities about extended release formulations Do not crush! Long acting preps available for PEG tubes If utilizing long acting preparations, may still need breakthrough doses i.e. not crushing the sustained release formulations!! There are sustained released formulations that can be used in a PEG tube etc�i.e. not crushing the sustained release formulations!! There are sustained released formulations that can be used in a PEG tube etc�

56. Pain Management and Older Adults Prescribing decisions based on - chronicity of pain - severity of pain - type of pain - other p-dynamic and p-kinetic concerns - side effect profiles And the geriatrician�s mantra - START LOW AND GO SLOW

57. Pain Management and Older Adults Need frequent re-assessment - effectiveness of analgesia - ADLs/ functional status - adverse effects constipation - ? unusual behaviors may be a sign of an adverse drug effect

58. �If we know that pain and suffering can be alleviated, and we do nothing about it, then we ourselves become the tormentors.�  Primo Levi�I must die. But must I die groaning?� Epictetus, 135 AD

59. Acknowledgements/ References AGS Panel on Persistent Pain in Older Persons, �The Management of Persistent Pain in Older Persons, JAGS, 50:S205-224, 2002. Dr. Karin Porter-Williamson, Medical Director of Palliative Care Consultation Team at KUMC Ballantyne and Mao, Opioid Therapy for Chronic Pain, NEJM, 349:20, Nov. 2003. Burris J, �Pharmacologic Approaches to Geriatric Pain Management,� Arch Phys Med Rehabil Vol 85, Suppl. 3, July 2004. Chodosh J et al,� Quality Indicators for Pain Management in Vulnerable Elders,� Annals of Internal Medicine, Vol. 135 No.8, Oct. 16, 2001. Dworkin et al, �Pharmacologic Treatment of Chronic Pain in Elderly�, Annals of Long-Term Care, 12(6):S1-S10, 2004. Fick et al, Upadating the Beers Criteria for Potentially Inappropriate Medications in Older Adults, Archives of Internal Medicine, Vol. 163, Dec. 2003. Fine P., �Pharmacological Management of Persistent Pain in Older Adults,� Clin J Pain, Vol 20 No.4, July/August 2004. Journal of the American Geriatrics Society 50:S205-S224, 2002 Podichetty et al, Chronic non-malignant musculoskeletal pain in older adults: clinical issues and opioid intervention, Postgraduate Medicine, 2003. Schneider J, Chronic pain management in older adults, Geriatrics, 60:5, May 2005. Zwakhalen S et al, �Pain in elderly people with severe dementia: A systematic review of behavioural pain assessment tools,� BMC Geriatrics, Vol6, No.3, Jan. 2006.